Meurer William J, Barsan William G
Department of Emergency Medicine, University of Michigan, Ann Arbor, Michigan, USA; Department of Neurology, University of Michigan, Ann Arbor, Michigan, USA.
Department of Emergency Medicine, University of Michigan, Ann Arbor, Michigan, USA.
World Neurosurg. 2014 Sep-Oct;82(3-4):e541-6. doi: 10.1016/j.wneu.2013.06.017. Epub 2013 Jul 9.
Effective treatments for acute neurologic illness and injury are lacking, particularly for spinal cord injury (SCI). The very structure of clinical trials may be contributing to this because assumptions made during trial planning preclude additional learning within residual important areas of uncertainty, such as dose, timing, and duration of treatment. Adaptive clinical trials offer potential solutions to some of the factors that may be slowing the pace of discovery. Broadly defined, one can consider an adaptive clinical trial as any sort of clinical trial that makes use of information from within the trial to make decisions about how the trial is conducted going forward; however, it is important to emphasize that regardless of the degree of flexibility or complexity of an adaptive clinical trial design, the types of designs being described are only those in which all potential changes to the conduct of the trial are prospectively defined before the first patient is enrolled. Within this review, we describe the structure of flexible adaptive clinical trial designs, the process by which they are developed and conducted, and potential opportunities and drawbacks of these approaches. We must accept that there are some uncertainties that remain when both exploratory and confirmatory trials are designed. The process by which teams carefully consider which uncertainties are most important and most likely to potentially compromise the ability to detect an effective treatment can lead to trial designs that are more likely to find the right treatment for the right population of patients.
目前缺乏针对急性神经疾病和损伤的有效治疗方法，尤其是脊髓损伤（SCI）。临床试验的结构本身可能就是造成这种情况的原因之一，因为在试验规划过程中做出的假设排除了在剩余重要不确定性领域（如治疗剂量、时间和持续时间）进行进一步研究的可能性。适应性临床试验为一些可能减缓发现速度的因素提供了潜在的解决方案。广义地说，适应性临床试验可以被视为任何利用试验中获得的信息来决定后续试验如何进行的临床试验；然而，需要强调的是，无论适应性临床试验设计的灵活性或复杂性程度如何，这里所描述的设计类型仅指那些在首位患者入组前就前瞻性地定义了试验实施过程中所有潜在变化的设计。在本综述中，我们描述了灵活适应性临床试验设计的结构、其开发和实施过程，以及这些方法的潜在机会和缺点。我们必须承认，在设计探索性试验和验证性试验时，仍然存在一些不确定性。团队仔细考虑哪些不确定性最为重要且最有可能影响检测有效治疗方法的能力的过程，能够产生更有可能为合适的患者群体找到正确治疗方法的试验设计。
